Intermittent Androgen Deprivation as Effective as Continuous Therapy after Radiotherapy

Many studies have shown that cyclic androgen deprivation is associated with a reduction in toxic effects in patients with prostate cancer. Results of a new international study show that the use of intermittent androgen treatment after radiotherapy in patients with elevated prostate-specific antigen (PSA) levels is noninferior to continuous androgen treatment and leads to improvements in some QOL measures (Crook JM, et al. N Engl J Med. 2012;367:895-903).

This is the first randomized trial to compare intermittent androgen deprivation treatment with continuous androgen treatment in patients with rising PSA levels after radiotherapy for prostate cancer, using OS as the primary end point. A total of 1368 patients with a PSA level >3 ng/mL more than 1 year after radiotherapy for localized prostate cancer were randomized to intermittent treatment with a luteinizing hormone–releasing hormone agonist combined with a nonsteroidal antiandrogen (N = 690) or to continuous treatment with the combination or with an orchiectomy (N = 696). The intermittent therapy was administered in 8-month cycles; nontreatment periods were determined by the patient’s PSA level.

The median follow-up was 6.9 years. No significant differences were seen between the groups. A total of 268 pros­tate cancer–related deaths occur­red in the intermittent-treatment group and 256 in the continuous-treatment group; the median OS was 8.8 years versus 9.1 years, respectively (hazard ratio for death, 1.02; 95% CI, 0.86-1.21).

In addition, some QOL measures were better with intermittent than with continuous treatment—symptom-related items were significantly improved, including hot flashes (P <.001), the desire for sexual activity (P <.001), and urinary symptoms (P = .006), with a trend toward im­provement in fatigue level (P = .07); by contrast, although functional domain scores were slightly higher, the difference was not significant.

Toxicity events were not significantly different between the groups. The study was terminated early when the prespecified noninferiority threshold for intermittent treatment was met.